[Risk factors of cytomegalovirus infection in patients with failed corneal grafts].

Objective: To investigate the levels of cytomegalovirus (CMV) infection and associated risk factors in corneal transplant recipients who experienced transplant failure. Methods: This was a case-control study. Clinical data from 576 cases (576 eyes) of patients who underwent repeat corneal transplant surgery at the Department of Ophthalmology, Peking University Third Hospital, due to corneal transplant failure from January 2016 to May 2022 were collected. Of these, 305 were male and 271 were female, with a median age of 44.0 (0.7, 91.0) years. The CMV infection rate was analyzed based on the detection of CMV DNA in aqueous humor or corneal tissue during corneal transplant surgery. Patients were divided into the CMV group (CMV DNA positive) and the control group (herpes virus DNA negative). The main research indicators included the CMV infection rate, clinical characteristics, and risk factors in corneal transplant recipients. Chi-square tests and binary logistic analysis were used to compare differences between the two groups in general information, systemic diseases, ocular lesions, ocular surgical history, and local and systemic medications. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for each CMV infection risk factor. Results: The overall CMV infection rate was 21.9%(126/576), with annual rates ranging from 10.9% to 37.7% from 2016 to 2021. After applying inclusion and exclusion criteria, 378 patients were included in the control trial, with 126 in the CMV group and 252 in the control group. Statistically significant differences between the two groups were observed in systemic immune-related corneal lesions [CMV group: 38 (30.2%), control group: 26 (10.3%)], local immune and inflammatory corneal lesions [CMV group: 46 (36.5%), control group: 40 (15.9%)], congenital corneal opacity [CMV group: 46 (36.5%), control group: 48 (19.0%)] total number of corneal transplants (CMV group: 178 times, control group: 276 times), corneal deep neovascularization crossing the graft [CMV group: 104 (82.5%), control group: 68 (27.0%)] and severe opacity [CMV group: 44 (34.9%), control group: 30 (11.0%)]. Binary logistic regression analysis showed that systemic immune-related corneal lesions (OR=4.044, 95%CI 1.810-9.033, P<0.001), local immune and inflammatory corneal lesions (OR=3.554, 95%CI 1.569-8.052, P=0.002), congenital corneal opacity (OR=2.606, 95%CI 1.216-5.589, P=0.014), total number of corneal transplants (OR=3.206, 95%CI 1.753-5.864, P<0.001), corneal deep neovascularization crossing the graft (OR=8.347, 95%CI 3.967-17.559, P<0.001), and severe opacity (OR=3.063, 95%CI 1.221-7.682, P=0.017) were independent risk factors for CMV infection after corneal transplant. Conclusions: CMV infection was present in more than 1/5 of corneal transplant recipients who experienced transplant failure. CMV infection after corneal transplant may be related to immune rejection reactions and ocular inflammatory responses. Inflammatory corneal lesions associated with systemic or local immune abnormalities, congenital corneal opacity, and multiple corneal transplants may exacerbate the levels of inflammatory factors during the perioperative period of corneal transplant, increasing the risk of post-transplant CMV infection, leading to the infiltration of deep neovascularization and severe opacity in the cornea.

[Analysis of prognosis and influencing factors of No. 253 lymph node metastasis in descending colon, sigmoid colon, and rectal cancer: a multicenter study].

Objectives: To analyze the influencing factors of No. 253 lymph node metastasis in descending colon cancer, sigmoid colon cancer, and rectal cancer, and to investigate the prognosis of No. 253 lymph node-positive patients by propensity score matching analysis. Methods: A retrospective analysis was performed on clinical data from patients with descending colon cancer, sigmoid colon cancer, rectosigmoid junction cancer, and rectal cancer who underwent surgery between January 2015 and December 2019 from the Cancer Hospital of the Chinese Academy of Medical Sciences, China-Japan Friendship Hospital, Peking Union Medical College Hospital, General Hospital of the Chinese People's Liberation Army, and Peking University Cancer Hospital. A total of 3 016 patients were included according to inclusion and exclusion criteria, comprising 1 848 males and 1 168 females, with 1 675 patients aged≥60 years and 1 341 patients aged<60 years. Clinical and pathological factors from single center data were subjected to univariate analysis to determine influencing factors of No. 253 lymph node metastasis, using a binary Logistic regression model. Based on the results of the multivariate analysis, a nomogram was constructed. External validation was performed using data from other multicenter sources, evaluating the effectiveness through the area under the receiver operating characteristic curve and the calibration curve. Using data from a single center, the No. 253 lymph node-positive group was matched with the negative group in a 1∶2 ratio (caliper value=0.05). Survival analysis was performed using the Kaplan-Meier method and Log-rank test. The Cox proportional hazards model was used to determine independent prognostic factors. Results: (1) The tumor diameter≥5 cm (OR=4.496,95%CI:1.344 to 15.035, P=0.015) T stage (T4 vs. T1: OR=11.284, 95%CI:7.122 to 15.646, P<0.01), N stage (N2 vs. N0: OR=60.554, 95%CI:7.813 to 469.055, P=0.043), tumor differentiation (moderate vs. well differentiated: OR=1.044, 95%CI:1.009 to 1.203, P=0.044; poor vs. well differentiated: OR=1.013, 95%CI:1.002 to 1.081, P=0.013), tumor location (sigmoid colon vs. descending colon: OR=9.307, 95%CI:2.236 to 38.740, P=0.002), pathological type (mucinous adenocarcinoma vs. adenocarcinoma: OR=79.923, 95%CI:15.113 to 422.654, P<0.01; signet ring cell carcinoma vs. adenocarcinoma: OR=27.309, 95%CI:4.191 to 177.944, P<0.01), and positive vascular invasion (OR=3.490, 95%CI:1.033 to 11.793, P=0.044) were independent influencing factors of No. 253 lymph node metastasis. (2) The area under the curve of the nomogram prediction model was 0.912 (95%CI: 0.869 to 0.955) for the training set and 0.921 (95%CI: 0.903 to 0.937) for the external validation set. The calibration curve demonstrated good consistency between the predicted outcomes and the actual observations. (3) After propensity score matching, the No. 253 lymph node-negative group did not reach the median overall survival time, while the positive group had a median overall survival of 20 months. The 1-, 3- and 5-year overall survival rates were 83.9%, 61.3% and 51.6% in the negative group, and 63.2%, 36.8% and 15.8% in the positive group, respectively. Multivariate Cox analysis revealed that the T4 stage (HR=3.067, 95%CI: 2.357 to 3.990, P<0.01), the N2 stage (HR=1.221, 95%CI: 0.979 to 1.523, P=0.043), and No. 253 lymph node positivity (HR=2.902, 95%CI:1.987 to 4.237, P<0.01) were independent adverse prognostic factors. Conclusions: Tumor diameter ≥5 cm, T4 stage, N2 stage, tumor location in the sigmoid colon, adverse pathological type, poor differentiation, and vascular invasion are influencing factors of No. 253 lymph node metastasis. No. 253 lymph node positivity indicates a poorer prognosis. Therefore, strict dissection for No. 253 lymph node should be performed for colorectal cancer patients with these high-risk factors.

[The efficacy and safety of nerve loop blocking in the treatment of blepharospasm in Meige syndrome].

Objective: To evaluate the efficacy and safety of nerve loop blocking in the treatment of blepharospasm caused by Meige syndrome. Methods: It was a retrospective case series study. Patients with Meige syndrome characterized by blepharospasm or blepharospasm-oromandibular dystonia who underwent nerve loop blocking in the Ophthalmology Department of Henan No. 3 Provincial People's Hospital from April 2018 to January 2020 were included. Before and after surgery, blepharospasm was graded, and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to score the symptoms of ocular and oral dystonia. The improvement rate of ocular spasm was calculated after surgery according to the scores. The postoperative complications were observed. The Wilcoxon rank test was used to compare the BFMDRS movement subscale scores before and after surgery. The independent sample Mann-Whitney U test was used to compare the improvement rates of eye spasm between male and female patients and between patients with and without combined oromandibular dystonia. Results: Among the 199 patients included, 64 (32.2%) were males, and 135 (67.8%) were females, aged 58 (51, 64) years (22-79 years). The postoperative follow-up period was 24 (21, 28) months. Preoperatively, blepharospasm was graded as grade 3 in 12 patients (6.0%) and grade 4 in 187 patients (94.0%), while the postoperative blepharospasm grades were grade 0 in 100 patients (50.3%), grade 1 in 64 patients (32.2%), grade 2 in 31 patients (15.6%), and grade 3 in 4 patients (2.0%). There was statistically significant difference in the BFMDRS scores of ocular dystonia before and after surgery [8.0 (8.0, 8.0) vs. 0.0 (0.0, 1.0); Z=-12.41, P<0.001]. The improvement rate of blepharospasm in all patients was 100% (87.5%, 100%), ranging from 43.8% to 100%, with no statistically significant difference between patients of different genders and between patients with and without combined oral dystonia (both P>0.05). Statistically significant difference existed in the scores of oral dystonia before and after surgery [2.0 (0.5, 4.5) vs. 1.0 (0.5, 2.0); Z=-4.38, P<0.001], with 25 of 65 patients (38.5%) having their oral symptoms improved. Postoperative complications included eyelid valgus (7.5%, 15/199), frontal numbness (100%, 199/199) and tearing (89.9%, 179/199). Conclusion: Nerve loop blocking is a relatively safe and effective method in the treatment of blepharospasm symptoms of Meige syndrome.

[Quality of life and influencing factors of postoperative accelerated rehabilitation of esophageal cancer patients].

Objective: To explore the quality of life and its influencing factors of enhanced recovery after surgery (ERAS) of esophageal cancer patients. Methods: The quality of life of 134 esophageal cancer patients was assessed using the quality of life assessment scale (EORTC QLQ-C30) developed by the European Cancer Research and Treatment Organization. Student's t test, One-way ANOVA and multiple linear regression statistical methods were used to analyze the effects of sociodemographic and clinical characteristics on patients' quality of life. Results: The overall score of quality of life (74.00) was lower than that of the general population (75.30). However, the scores of emotion and cognition in function dimension (93.97 and 95.77) were better than those of the general population (82.80 and 86.50). The results of fatigue, pain, insomnia and constipation in symptom dimension (14.18, 10.94, 11.69 and 5.72) were better than those of the general population (28.80, 20.50, 20.40 and 10.70). The pathological stage, body mass index and dietary were independent influencing factors for the quality of life of patients with esophageal cancer (P<0.05). Conclusions: ERAS can partially improve the quality of life of esophageal cancer patients. More attention should be paid to the esophageal cancer patients after surgery and take targeted measures to improve their quality of life.

[SENP1 induced protein deSUMO modification increased the chemotherapy sensitivity of endometrial cancer side population cells].

Objective: To inhibit the stemness maintenance potential of endometrial cancer and increase the sensitivity of endometrial cancer side population cells to chemotherapy drugs by inducing extensive deSUMOylation modification of proteins. Methods: Flow cytometry was used to sort and culture CD133(+) CD44(+) KLE endometrial cancer cell clone spheres. Protein expression level of small ubiquitin-related modifier 1 (SUMO1) and two stemness maintenance genes of tumor side population cells, octamer binding transcription factor-4 (Oct4) and sex determining region Y-box2 (Sox2), were detected by western blotting method. Lentivirus-mediated Sentrin/SUMO-specific proteases 1 (SENP1) gene was stably transfected into KLE side population cells. Western blotting was used to detect the protein expressions of SENP1, SUMO1, Oct4 and Sox2. The clone formation rate was compared between KLE side population cells with or without SENP1 overexpression. Flow cytometry was applied to detect cell cycle changes. 3-(4, 5-Dimethylthiazole-2)-2, 5-diphenyl-tetrazolium bromide (MTT) experiment and flow cytometry apoptosis method were used to detect the chemosensitivity of the side population of endometrial cancer cells to cisplatin. Tumor-bearing mouse models of endometrial cancer were established to detect the effect of SENP1 overexpression on the chemotherapy sensitivity of cisplatin. Results: Compared with CD133(-)CD44(-) KLE cells, CD133(+) CD44(+) KLE side population cells could form clonal spheres and express higher levels of SUMO1, Oct4 and Sox2 proteins (P<0.05). Compared with KLE side population cells that were not transfected with SENP1 gene, the expression level of SENP1 protein in KLE side population cells overexpressing SUMO1、Oct4 and Sox2 were lower. The clonal sphere formation rate was reduced from (25.67±5.44)% to (7.46±1.42)%, and cell cycle shifted from G(0)/G(1) phase to G(2) phase. IC(50) of cisplatin decreased from (55.46±6.14) µg/ml to (11.55±3.12) µg/ml, and cell apoptosis rate increased from (9.76±2.09)% to (16.79±3.44)%. Overexpression of SENP1 could reduce the tumorigenesis rate of KLE side population cells in vivo and increase their chemotherapy sensitivity to cisplatin (P<0.05). Conclusion: Overexpression of SENP1 can induce protein deSUMOylation modification, inhibit the stemness maintenance potential of endometrial cancer side population cells, and enhance their chemotherapy sensitivity, which provides a new reference for gene therapy of endometrial cancer.

[Application of pretrained model based on electronic medical record in recognition of acute respiratory infection].

Objective: To evaluate the recognition of acute respiratory infection (ARI) by a pretrained model based on electronic medical records (EMRs). Methods: 38 581 EMRs were obtained from Chongqing University Three Gorges Hospital in December 2021. Bidirectional encoder representation from transformers (BERT) pretrained model was used to identify ARI in EMRs. The results of medical professionals were considered as the gold standard to calculate the sensitivity, specificity, Kappa value, and area under the curve of the receiver operating characteristic (AUC). Results: There were 3 817 EMRs in the test set, with 1 200 ARIs. A total of 1 205 cases were determined as ARI by the model, with a sensitivity of 92.67% (1 112/1 200) and a specificity of 96.45% (2 524/2 617). The model identified ARI with similar accuracy in males and females (AUCs 0.95 and 0.94, respectively), and was more accurate in identifying ARI cases in those aged less than 18 than in adults 18-59 and adults 60 and older (AUCs 0.94, 0.89 and 0.94, respectively). The current model had a better identification of ARIs in outpatient patients than that in hospitalized patients, with AUCs of 0.74 and 0.95, respectively. Conclusion: The use of the BERT pretrained model based on EMRs has a good performance in the recognition of ARI cases, especially for the outpatients and juveniles. It shows a great potential to be applied to the monitoring of ARI cases in medical institutions.

[Clinical characteristics and diagnosis and treatment strategies of patients with severe traumatic aortic injury].

Objective: To investigate the clinical characteristics and diagnosis and treatment strategies of patients with severe traumatic aortic injury (TAI). Methods: A total of 25 patients with TAI, who hospitalized in our hospital between August 2005 to March 2021 and underwent thoracic aortic endovascular repair (TEVAR), were included in this retrospective study. According to the time from admission to TEVAR, the patients were divided into emergency TEVAR group (14 cases, TEVAR within 24 h of admission) and elective TEVAR group (11 cases, patients underwent surgery or fracture reduction and fixation first for serious injuries and then underwent TEVAR more than 24 h after admission). The general clinical data of patients, injury severity score (ISS), time from admission to intervention, total hospital stay, the proportion of closed chest drainage and the proportion of abdominal organ repair were obtained and compared. Clinical follow-up and 1-year postoperative aortic computed tomography angiography (CTA) were performed on the patients. Death, the occurrence of aortic adverse events and injury recovery were followed up and recorded. Results: The mean age of these 25 TAI patients was (41.4±14.4) years, 20 patients were males (80.0%). 21 patients (84.0%) had persistent chest and back pain, 17 (68.0%) had pleural effusion and 5 (20.0%) had mediastinal hematoma. The injury severity score (ISS) was significantly higher in the elective TEVAR group than in the emergency TEVAR group (24.9±14.4 vs. 35.5±9.3, P=0.044). The time from admission to intervention ((1.0±0.0) d vs. (3.4±0.9) d, P<0.001], the time from admission to TEVAR ((1.0±0.0) d vs. (11.5±13.8) d, P=0.030) and total hospital stay ((6.1±2.3) d vs. (26.8±7.7) d, P<0.001) were significantly longer in elective TEVAR group than in emergency TEVAR group. The proportion of thoracic closed drainage was significantly lower in the elective TEVAR group than in the emergency TEVAR group (9 (64.3%) vs. 2 (18.2%), P=0.042). The proportion of abdominal organ repair was significantly higher than in the emergency TEVAR group (0 vs. 4 (36.4%), P=0.026). All of 25 patients were discharged alive and followed up for (84.0±30.5) months. All patients survived and completed 1-year postoperation CTA. There were no aortic adverse events occurred, and no complications after surgery, and the fractures and organ injuries healed well. Conclusions: The clinical characteristics of severe TAI are acute multi-injuries combined with persistent chest and/or back pain, pleural effusion, and mediastinal hematoma. Timely diagnosis and treatment are important factors for the outcome. The treatment strategy for multi-injuries should give priority to dealing with life-threatening injuries. TEVAR is the primary treatment strategy for severe TAI and is related to satisfactory outcomes.

[Safety and efficacy of ultrafiltration on heart failure patients with reduced ejection fraction and diuretic resistance: results from a single-center randomized controlled trial].

Objective: To investigate the safety and efficacy of ultrafiltration on diuretic sensitivity in heart failure patients with reduced ejection fraction and diuretic resistance. Methods: This was a single-center randomized controlled trial. A total of 148 heart failure patients with reduced ejection fraction admitted to the Hospital of Traditional Chinese Medicine of Xinjiang Uygur Autonomous Region from June 2010 to June 2020 were enrolled in this study, and these patients were randomly divided (ratio 1:1) into the ultrafiltration group (n=74) and the control group (n=74). All patients were treated with diuretics, cardiotonic, vasodilator and other comprehensive drugs according to relevant guidelines. After grouping, the patients in the control group were treated with standard treatment plan, while patients in the ultrafiltration group were treated with ultrafiltration on top of standard therapy. Diuretic drugs were discontinued during ultrafiltration, and intravenously furosemide (40 mg) was given immediately and 24 hours after the end of ultrafiltration. Clinical data including gender, age, complicated diseases, New York Heart Association (NYHA) function classification, etc. were collected. Effectiveness indicators include urine volume (the first 12-hour and 24-hour urine volume and the second 24-hour urine volume after using diuretic), body weight and dyspnea severity score. Safety indicators include systolic blood pressure, serum creatinine, serum Na+ concentration, blood K+ concentration and the number of deaths before and after intervention. Results: Two patients in the control group died due to worsening heart failure after randomization and were excluded in this study, 146 patients were finally analyzed (72 patients in the control group and 74 patients in the ultrafiltration group). There were 93 males, and the age was (68.3±11.2) years. There was no significant difference between patients in the ultrafiltration group and the control group in gender, age, body weight, course of disease, dyspnea severity score, NYHA function classification Ⅲ/Ⅳ, the proportion of patients with severe edema of both lower limbs, the proportion of patients with complicated diseases, and basic medication (all P>0.05). After using diuretics, the urine volume of the first 12-hour and 24-hour and the second 24-hour were significantly higher in the ultrafiltration group than in the control group (all P<0.05). Body weight decreased significantly after ultrafiltration treatment as compared with that before intervention in the ultrafiltration group (P<0.05). Compared with the control group, the dyspnea severity score was significantly improved in the ultrafiltration group (P<0.05). There was no significant difference in systolic blood pressure, serum creatinine, serum Na+ concentration, blood K+ concentration of patients between ultrafiltration group and control group before and after intervention (all P>0.05). During the clinical diagnosis and treatment, 2 male patients in the control group died, and the cause of death was aggravation of basic diseases complicated with acute heart failure and cardiogenic shock. There was no death in the ultrafiltration group, and there were no obvious clinical adverse events during and after ultrafiltration. Conclusion: Ultrafiltration therapy is safe and can improve diuretic sensitivity in heart failure patients with reduced ejection fraction and diuretic resistance.

[Comparison study of whole exome sequencing and targeted panel sequencing in molecular diagnosis of inherited retinal dystrophies].

OBJECTIVE: To evaluate and compare whole exome sequencing (WES) and targeted panel sequencing in the clinical molecular diagnosis of the Chinese families affected with inherited retinal dystrophies (IRDs). METHODS: The clinical information of 182 probands affected with IRDs was collected, including their family history and the ophthalmic examination results. Blood samples of all probands and their relatives were collected and genomic DNA was extracted by standard protocols. The first 91 cases were subjected to the WES and the other 91 cases were subjected to a specific hereditary eye disease enrichment panel (HEDEP) designed by us. All likely pathogenic and pathogenic variants in the candidate genes were determined by Sanger sequencing and co-segregation analyses were performed in available family members. Copy number variations (CNVs) detected by HEDEP were further validated by multiplex ligation-dependent probe amplification (MLPA). As PRGR ORF15 was difficult to capture by next generation sequencing (NGS), all the samples were subjected to Sanger sequencing for this region. All sequence changes identified by NGS were classified according to the American College of Medical Gene-tics and Genomics and the Association for Molecular Pathology (ACMG/AMP) variant interpretation guidelines. In this study, only variants identified as pathogenic or likely pathogenic were included, while those variants of uncertain significance, likely benign or benign were not included. RESULTS: In 91 cases with WES, pathogenic or likely pathogenic variants were determined in 30 cases, obtaining a detection rate of 33.00% (30/91); While in 91 cases with HEDEP sequencing, pathogenic or likely pathogenic variants were determined in 51 cases, achieving the diagnostic rate of 56.04% (51/91), and totally, the diagnostic rate was 44.51%. HEDEP had better sequencing coverage and read depth than WES, therefore HEDEP had higher detection rate. In addition, HEDEP could detect CNVs. In this study, we detected disease-causing variants in 29 distinct IRD-associated genes, USH2A, ABCA4 and RPGR were the three most common disease-causing genes, and the frequency of these genes in Chinese IRDs population was 11.54% (21/182), 6.59% (12/182) and 3.85% (7/182), respectively. We found 43 novel variants and 6 cases carried variants in RPGR ORF15. CONCLUSION: NGS in conjunction with Sanger sequencing offers a reliable and effective approach for the genetic diagnosis of IRDs, and after evaluating the pros and cons of the two sequencing methods, we conclude that HEDEP should be used as a first-tier test for IRDs patients, WES can be used as a supplementary molecular diagnostic method due to its merit of detecting novel IRD-associated genes if HEDEP or other methods could not detect disease-causing va-riants in reported genes. In addition, our results enriched the mutational spectra of IRDs genes, and our methods paves the way of genetic counselling, family planning and up-coming gene-based therapies for these families.

[Effect of polyphyllin â ¡ on the proliferation, invasion and chemosensitivity to temozolomide of glioma cells].

Objective: To investigate the effect and mechanism of Polyphyllin Ⅱ on the proliferation, invasion and chemosensitivity of glioma cells. Method: CCK-8 cell proliferation assays and Transwell assays were employed to determine the effect of Polyphyllin Ⅱ on the proliferation and invasion of glioma cells (T98G and LN18), respectively. The expression of E-cadherin, Snail and O6-methylguanine DNA methyltranferase (MGMT) were quantified by Western blot analysis. Results: Polyphyllin Ⅱ could inhibit the proliferation of glioma cells in a time- and does-dependent manner. The half maximal inhibitory concentration (IC(50)) of T98G at 24 h, 48 h and 72 h were (5.82±0.32), (3.57±0.07) and (1.48±0.35) µmol/L, respectively. The IC(50) of LN18 at 24 h, 48 h and 72 h were (6.83±0.11), (4.28±0.29), (2.66±0.22) µmol/L, respectively. After being treated with 2 µmol/L, 4 µmol/L and 6 µmol/L Polyphyllin Ⅱ for 24 h, the percentage of invasive cell area in the chamber area was lower than those in T98G and LN18 control groups (P<0.05). Western blot analysis showed that compared with glioma cells without Polyphyllin Ⅱ treatment, the expression of E-cadherin in T98G and LN18 was higher (F=85.56, P<0.05; F=60.80, P<0.05), but the expression of snail was lower (F=25.34, P<0.05; F=48.28, P<0.05). When temozolomide was used in combination with Polyphyllin Ⅱ at different concentrations, the coefficient of drug interaction (CDI) was less than 1. Western blot showed that MGMT expressions in T98G and LN18 were inhibited compared with glioma cells without Polyphyllin Ⅱ treatment (F=40.38, P<0.05; F=48.44, P<0.05). Conclusion: Polyphyllin Ⅱ can inhibit the proliferation and invasion of glioma cells, and improve its sensitivity to Temozolomide.

[Analysis of clinical, pathological features and therapeutic treatments in predicting prognosis of elderly glioblastomas].

Objective: This study was designed to investigate prognostic factors and the potential relationship between the expression of Ki67 and IDH of glioblastoma in the elderly (≥ 65 years old) and the clinical factors such as gender, the KPS score and treatments including surgical resection, radiotherapy and chemotherapy and the prognosis of such patients. Methods: Fifty-four elderly patients (≥ 65 years old) with glioblastoma admitted to the First Affiliated Hospital of Zhengzhou University from 2013 to 2018 were enrolled in this study. The expression of Ki67 was detected by immunohistochemical SP method and the mutation of IDH was detected by Sanger sequencing. Finally, statistical analysis was performed to determine whether Ki67, the mutation of IDH, gender, the KPS score and the extent of resection, radiotherapy and chemotherapy were associated with the clinical prognosis of the patients. Results: Of the 54 elderly patients with glioblastoma, none was detected with IDH mutation. Univariate analysis showed that Ki67(P=0.033), the KPS score (P=0.008), the extent of resection (P<0.001) were factors influencing the prognosis of elderly patients with glioblastoma. Patients receiving postoperative adjuvant radiotherapy (P=0.002) and chemotherapy (P=0.034) had longer survival time. There was no significant correlation between gender (P=0.467) and prognosis. Multivariate analysis demonstrated that radiotherapy (OR 2.446, P=0.009) and the extent of resection (OR 6.976, P<0.001) were independent prognostic factors. Conclusions: No IDH mutation was detected in all the patients in this study, indicating that IDH mutation is indeed rare in elderly glioblastoma, which suggests that geriatric population often harbor a molecular phenotype with poor prognosis. Ki67, KPS score, the extent of resection, radiotherapy and chemotherapy were the factors influencing the prognosis of patients.

[A pathological report of three COVID-19 cases by minimal invasive autopsies].

Objective: To investigate the pathological characteristics and the clinical significance of novel coronavirus (2019-nCoV)-infected pneumonia (termed by WHO as coronavirus disease 2019, COVID-19). Methods: Minimally invasive autopsies from lung, heart, kidney, spleen, bone marrow, liver, pancreas, stomach, intestine, thyroid and skin were performed on three patients died of novel coronavirus pneumonia in Chongqing, China. Hematoxylin and eosin staining (HE), transmission electron microcopy, and histochemical staining were performed to investigate the pathological changes of indicated organs or tissues. Immunohistochemical staining was conducted to evaluate the infiltration of immune cells as well as the expression of 2019-nCoV proteins. Real time PCR was carried out to detect the RNA of 2019-nCoV. Results: Various damages were observed in the alveolar structure, with minor serous exudation and fibrin exudation. Hyaline membrane formation was observed in some alveoli. The infiltrated immune cells in alveoli were majorly macrophages and monocytes. Moderate multinucleated giant cells, minimal lymphocytes, eosinophils and neutrophils were also observed. Most of infiltrated lymphocytes were CD4-positive T cells. Significant proliferation of type Ⅱ alveolar epithelia and focal desquamation of alveolar epithelia were also indicated. The blood vessels of alveolar septum were congested, edematous and widened, with modest infiltration of monocytes and lymphocytes. Hyaline thrombi were found in a minority of microvessels. Focal hemorrhage in lung tissue, organization of exudates in some alveolar cavities, and pulmonary interstitial fibrosis were observed. Part of the bronchial epithelia were exfoliated. Coronavirus particles in bronchial mucosal epithelia and type Ⅱ alveolar epithelia were observed under electron microscope. Immunohistochemical staining showed that part of the alveolar epithelia and macrophages were positive for 2019-nCoV antigen. Real time PCR analyses identified positive signals for 2019-nCoV nucleic acid. Decreased numbers of lymphocyte, cell degeneration and necrosis were observed in spleen. Furthermore, degeneration and necrosis of parenchymal cells, formation of hyaline thrombus in small vessels, and pathological changes of chronic diseases were observed in other organs and tissues, while no evidence of coronavirus infection was observed in these organs. Conclusions: The lungs from novel coronavirus pneumonia patients manifest significant pathological lesions, including the alveolar exudative inflammation and interstitial inflammation, alveolar epithelium proliferation and hyaline membrane formation. While the 2019-nCoV is mainly distributed in lung, the infection also involves in the damages of heart, vessels, liver, kidney and other organs. Further studies are warranted to investigate the mechanism underlying pathological changes of this disease.

[Clinico-pathological features of temporal lobe epilepsy with enlarged amygdala].

OBJECTIVE: To summarize the clinical, video electroencephalogram (VEEG), radiological and pathological features of 3 patients of temporal lobe epilepsy (TLE) with amygdala enlargement (AE). METHODS: Three TLE patients with AE who were hospitalized in Peking University International Hospital were collected. The above features were retrospectively analyzed, and the amygdala volume was measured as well. RESULTS: Of all the 3 patients, 2 were females and 1 male, whose seizure onset ages varied from 21 to 40 years. Two cases presented with secondarily generalized tonicclonic seizures after falling asleep during the night. One of the 2 cases had complex partial seizures (CPSs) with episodic memory and automatism after one year, and the third one had CPSs with lip smacking and tongue wagging during the night. All the patients suffered from obvious anxious disorder. Unilateral AE by MRI was demonstrated in the 3 cases, one on the right side, and the other two on the left side. The average amygdala volume of the enlarged side and the other side were (2 123.7±131.8) mm3 and (1 276.3±156.9) mm3, respectively. Unilateral interictal epileptic discharges were ipsilateral to the AE in 2 cases, while the other patient showed bilateral interictal epileptic discharges. The ictal VEEG showed that the seizure onset zone was ipsilateral to the AE and was confined to the anterior and middle temporal regions in the 3 patients. The interictal single-photon emission computed tomography (SPECT) was negative in 2 cases. The interictal positron emission tomography (PET) showed hypometabolism in the AE in one case. The histological pathology revealed focal cortical dysplasia in the amygdala and temporal lobe in the 3 cases, and one of the 3 cases was combined with hippocampal sclerosis. All the patients became seizure free after surgery in the half year following-up. VEEG revealed slow wave activity and occasional spike wave in the operated side. CONCLUSION: AE may be one subtype of TLE. It is necessary to recognize AE in TLE with MRI-negative. For those poorly responsive to antiepileptic drugs, surgical treatment could provide a better solution. Focal cortical dysplasia may be one of the most common pathological features of TLE with AE.

[IDH、TERT and 1p/19q predicting clinical outcomes in patients with anaplastic oligodendroglioma].

Objective: To investigate the prognostic values of IDH, TERT and 1p/19q in patients with anaplastic oligodendroglioma. Methods: In the study, 66 patients with pathological diagnosis of anaplastic oligodendroglioma were enrolled (The First Affiliated Hospital of Zhengzhou University 2011 to 2016 years). Kaplan-Meier method was used to calculate the survival rates. Log-rank was used to calculate the differences in group. Chi-square testwas used tocalculate the differences in common factor group. Cox regression model was used to conduct multivariate analysis. Results: The median survival time of IDH-wt and IDH-mt subgroups were 16.10 and 42.00 months with statistical significance (P=0.001). The median survival time of 1p/19q codeleted and 1p/19q noncodeleted subgroups were 42.00 and 22.40 months with statistical significance (P=0.012). IDH-mt and 1p/19q codeleted predicted better survivals compared with IDH-wt and 1p/19q noncodeleted (P=0.001). And IDH-mt and 1p/19q noncodeleted predicted better survivals compared with IDH-wt and 1p/19q noncodeleted (P=0.041), too. Multivariate survival analysis demonstrated that Molecular groups was an independent factor to evaluate the prognosis of anaplastic oligodendroglioma (P=0.008). Conclusion: IDH-mtand (or) 1p/19q codeletedpredicted better survivals in patients with anaplastic oligodendroglioma. IDH and 1p/19q deleted might be a biomarker for predicting prognosis of patients with anaplastic oligodendroglioma.

[Preoperative prognostic nutritional index predicts clinical outcomes in patients with lower-grade gliomas].

Objective: To investigate the prognostic values of preoperative prognostic nutritional index (PNI) in patients with lower-grade gliomas. Methods: In the study, 379 patients with pathological diagnosis of lower-grade gliomas were enrolledwhich were confirmed in The First Affiliated Hospital of Zhengzhou University (2011-02 to 2016-05). Kaplan-Meier method was used to calculate the survival rates. log-rank was used to calculate the differences in group. Cox regression model was used to conduct multivariate analysis. Results: The cutoff value of PNI was 46.70. The median survival time of PNI≤47.80 and PNI>47.80 subgroups were 46.76 and 67.37 months with statistical significance (P<0.001). High PNI predicted a better survival rate. Multivariate survival analysis demonstrated that low PNI was an independent risk factor to evaluate the prognosis of glioma patients. In lower-grade gliomas, high PNI predicted better survivals in TERT mutation only (P=0.003) and triple-negative group (P=0.007). Conclusion: In lower-grade gliomas, low PNI predicts worse survivals and PNI have differential prognostic significances in molecular groups of lower-grade gliomas.

[Resection of lumbar nerve sheath tumors via muscle-pedicle open-door laminoplasty approach].

Objective: To evaluate the efficacy and safety of resection of lumbar nerve sheath tumors via muscle-pedicle open-door laminoplasty approach. Methods: From March 2016 to June 2018, 6 patients (4 males and 2 females, average age (45±14) years) with lumbar spinal nerve sheath tumors received surgical treatment via muscle-pedicleopen-door laminoplasty approach in the Department of Spinal Surgery, the Affiliated Hospital of Qingdao University. The operation time, blood loss, cerebral spinal fluid (CSF) leakage, and pre- and post-operative Oswestry Disability Index (ODI) and low back and leg pain visual analogue scale (VAS) were recorded for all patients. Cobb angle of lumbar lordosis was measured on the standing lateral X-ray before and 6 months after surgery. Bone fusion was observed in computed tomography at six months after surgery. Results: Total tumor resection was achieved in all the 6 patients. The operation time was from 76 to 117 minutes (average, (102±15) minutes). The blood loss was from 160 to 280 ml (average, (256±24) ml). No CSF leakage was observed in this cohort.All patients were followed up for more than 6 months. ODI and VAS for low back and leg pain were much better at one month after operation than those before the operation(t=7.70, 8.63,11.31, all P<0.05). The Cobb angle of lumbar lordosis before operation and at six months after the operation were comparable in all six patients(t=0.70, P>0.05). Bone fusion was observed in computed tomography at six months after surgery. No bone necrosis or absorption, no lamina dislodgement or spinal stenosis was occurred. Conclusions: The muscle-pedicle open-door laminoplasty approach is proved effective and safe to incise nerve sheath tumors in the lumbar spine. Some blood supply of lamina can be kept intact to accelerate bone fusion.

[Clinical characteristics and microsurgical strategy of intracranial posterior circulation aneurysms].

Objective: To explore the clinical characteristics and microsurgical strategies of intracranial posterior circulation aneurysms. Methods: The clinical manifestations, imaging data, surgical approaches and follow-up results of 35 patients with circulating aneurysms (37 aneurysms) treated by microsurgery in the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2018 were analyzed retrospectively. Results: A total of 22 aneurysms were clipped, 13 were clipped and resected, 1 case was clipped and together with AVM resection and 1 case was isolated. Of 37 aneurysms in 35 patients, 11 aneurysms were at the basilar artery apexes, 10 at the posterior cerebral arteries, 6 at the posterior inferior cerebellar arteries, 3 at the basilar arteries, 3 at the vertebral arteries (including 1 case of vertebral arterial dissecting aneurysm), 2 at the anterior inferior cerebellar arteries and 2 at the superior cerebellar arteries. The surgical approaches included pterional approach, extensive pterional approach, infratemporal fossa approach, retrosigmoid approach and far-lateral approach. The Glasgow Outcome Scale (GOS) scores showed good recovery in 24 cases, moderate neurological dysfunction in 6 cases, severe neurological dysfunction in 2 cases, persistent vegetative state in 1 case and 2 cases of death 6 months after their discharge from hospital. Conclusions: Posterior circulation aneurysms are adjacent to important structures. They are deep in position, with small operation space and difficult to operate. Full preoperative evaluation of the condition, selection of appropriate surgical methods are the key factors to benefit the patients.

[Effect of GPX4 on proliferation and metastasis of renal clear cell carcinoma and its relationship with expression of IGF-1R and COX-2].

Objective: To investigate the effect of human glutathione peroxidase 4 (GPX4) on the proliferation and metastasis of renal clear cell carcinoma and its relationship with the expression of IGF-1R and COX-2. Methods: Culture of human normal tubular cell line HK-2 and human renal clear cell carcinoma Caki-1, A498, Caki-2, 786-o in vitro. Detection of GPX4 mRNA and protein expression in different cell lines by quantitative real-time PCR (RT-PCR) and Western blot assay. Overexpression of GPX4 cell lines, including blank carrier (Vector) and overexpress GPX4 (oeGPX4) group, and interference with GPX4 renal clear cell carcinoma cell lines, including random sequence (shControl), interference GPX4#1 (shGPX4#1) and interference GPX4#2 (shGPX4#2) group by lentiviral transfection. RT-PCR technology and Western blot were used to detect the expression of GPX4, IGF-1R and COX-2 mRNA and protein. CCK-8 assay was used to detect the relative proliferation of cells at 0, 24, 48, 72 and 96 h in each group. Transwell invasion and migration assay to detect the invasion and migration ability of cells of each group. Results: GPX4 is highly expressed in renal clear cell carcinoma cell lines compared to human normal tubular cell lines; The expression of GPX4, IGF-1R and COX-2 mRNA was significantly increased in oeGPX4 cells compared with Vector cells, the expression of GPX4,IGF-1R and COX-2 mRNA was significantly decreased in shGPX4#1 and shGPX4#2 compared with shControl cells; oeGPX4 cells significantly increased proliferative capacity compared to Vector cells at 72 and 96 h, the proliferation of shGPX4#1 and shGPX4#2 cells was significantly lower than that of shControl cells at 72 and 96 h; The number of invading and migrating cells of oeGPX4 cells was significantly higher than that of Vector cells, the number of invasive and migrating cells in shGPX4#1 and shGPX4#2 cells was significantly lower than that in shControl cells. Conclusion: GPX4 is highly expressed in renal clear cell carcinoma cells, which is positively correlated with the expression of IGF-1R and COX-2, and can promote cell proliferation and metastasis in vitro.

[Expression of dishevelled-2 in cartilage of rheumatoid arthritis and its effect on cartilage destruction].

Objective: To study the expression of dishevelled-2 (DVL2) in rheumatoid arthritis cartilage and its effect on cartilage destruction. Methods: Cartilage DVL2 expression in rat models of rheumatoid arthritis (RA), osteoarthritis(OA) and collagen-induced arthritis(CIA) were tested by Western blotting. DVL2 overexpressed lentivirus was transfected into the knee of CIA rats. Primary chondrocytes were extracted from RA patients by knee arthroplasty and transfected with DVL2 overexpressed lentivirus. Gene expression of related inflammation related cytokines was detected by real-time polymerase chain reaction (PCR) . Results: Compared with knee articular cartilage in OA patients and normal rats, DVL2 protein was highly expressed in knee cartilage of RA patients and CIA rats (P values 0.041 and 0.032, respectively). DVL2 did not significantly affect the destruction of knee cartilage in CIA rats (P=0.885). DVL2 overexpression in chondrocytes enhanced gene expression of cyclo-oxygenase-2 (COX-2), inducible nitric oxide synthase (NOS), matrix metalloproteinase (MMP) 2, MMP-3, and MMP-9, which could be more pronounced when tumor necrosis factor alpha was added. Conclusions: DVL2 is highly expressed in RA articular cartilage and promotes the expression of inflammatory cytokines and MMP gene in chondrocytes by activating Wnt/ß-catenin pathway, which involves in the destruction of articular cartilage in RA.

[Diagnosis and thoracoscopic treatment for pleuroperitoneal communication complicating peritoneal dialysis].

Objective: To evaluate the safety and efficacy of diagnosis and treatment of pleuroperitoneal communication in patients on peritoneal dialysis by computerized tomography (CT) peritoneography and thoracoscopic surgery. Methods: The records of 8 pleuroperitoneal communication patients treated by thoracoscopic surgery in Peking University First Hospital from January 2012 to March 2017 were retrospectively reviewed.CT peritoneography was performed before surgical treatment. Iopamiro (50 ml∶15 g) was mixed with 2 L of peritoneal dialysate solution, and then was instilled into the peritoneal cavity through the Tenckhoff catheter. After dwelling for 1 hour, CT scan was taken from thorax to upper abdomen.The thoracic cavity was filled with sterile saline, and then carbon dioxide was inflated to the peritoneal cavity via Tenckhoff catheter.Air bubbles leaking from the diaphragmatic defect were identified during thoracoscopic operation.Then defect was repaired and pleurodesis was performed. Results: The CT value of pleural effusion increased to (155±57) HU.Pleuroperitoneal communication was clearly diagnosed.The diaphragmatic defects in 5 cases were detected and repaired.However, defects in the other 3 cases were not found.The mean operative time was (152±50) minutes. All patients had uneventful recovery and reinstated normal peritoneal dialysis 3 weeks after the operation.The median follow-up time was 14.5 months (1-68 months) and no recurrence occurred. Conclusions: CT peritoneography could identify pleuroperitoneal communication clearly. Thoracoscopic surgery is a safe and reliable method for pleuroperitoneal communication and could restore patients to peritoneal dialysis.